To date, there have been no reports linking arachidonic acid (AA) metabolism with the pathobiology of specific humman tumor cell populations in pulmonary adenocarcinoma (PAC). The correlation of prostaglandin (PG) biosynthesis with teh pathobiology of PAC was studied by exploring the metabolism of AA in human lung carcinoma cell lines. Two PAC derived cell lines (NCI-H322 and NCI-H358) and two small cell carcinoma derived cell lines (NCI-H69 and NCI-H128) were used. No metabolism of AA occurred in either unstimulated or calcium ionophere A23187-stimulated NCI-H69 and NCI-H128 cells. The major metabolite of AA isolated from both NCI-H322 and NCI-H358 cells was identified as prostaglandin E2 (PGE2). The prostaglandin endoperoxide synthase (PES) activity expressed as immunoreactive PGE2, (pmole/min/mg protein) was found to be 10.3+ 0.28 and 4.8 + 0.48 in NCI-H358 and NCI-H322 cells, respectively. Production of PGE2 in both NCI-H358 and NCI-H322 cells was linear up to 10 min with apparent Km of 8.3 and 5.5 UpsilonM and Vmax of 12.5 and 5.3 pmole/min/mg protein for NCI-H358 and NCI-H322 cells, respectively. Moreover, PGE2 did not undergo further metabolism by either the NCI-H358 nor the MCI-H322 cells. Aspirin, inhibited PGE2 production of 78% and 50\ in NCI-H358 and NCI-H322 cells, respectively. In the presence of exogenous AA, A23187 stimulated PGE2 production in NCI-H322 cells by 76% without affecting the production of PGE2 in the NCI-H358 cells. In contrast, A23187 stimulated the endogenous production of PGE2 to a greater extent in both NCI-H322 and NCI-H358 cells. These results suggest that certain types of tumors within the category of human PAC may preferentially synthesize and release PGE2. This finding may be useful diagnostically since elevated PGE2 synthesis may be a characteristic unique to a group or subclass of PAC in patients. Furthermore, the human PAC lines can be employed as models to explore the ability of different human lung cancers to activate xenobiotics, especially antitumor agents directed at the PES system in hopes of achieving more selective therapeutic effectiveness.